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International Journal of Bioprinting Printed organoids for medicine

feedback loops between transforming growth factor-beta- Intriguingly, macrophage incorporation exacerbated
mediated matrix remodeling and tumor cell migration, peripheral cell resistance via interleukin-6/Janus kinase/
offering unprecedented resolution of microenvironmental signal transducer and activator of transcription 3 activation,
regulation. highlighting spatially compartmentalized stroma-tumor
interactions in therapeutic evasion. 152
Advanced 3D bioprinting platforms have achieved
precise reconstruction of spatial topology to organize triple- These models have demonstrated clinical utility in
negative breast cancer cells (MDA-MB-231) alongside predicting colorectal cancer liver metastasis patterns
stromal fibroblasts and endothelial cells by extrusion- (82% accuracy), optimizing anti-angiogenic dosing
based multi-nozzle bioprinting. This approach replicates regimens (37% survival extension in murine models, and
the cellular and TME diversity observed in native tumors, deconvoluting transforming growth factor-beta/receptor
preserving subclone viability and minimizing mechanical activator of nuclear factor-κB ligand synergy in breast
stress during printing. 25,84 Stratified deposition of KRAS- cancer bone niches. 149,153,154 Convergence with spatial omics
mutated and wild-type cells recapitulates in vivo spatial and smart biomaterials promises to reconstruct tumor
competition dynamics, mirroring the clonal hierarchy evolutionary landscapes at single-cell resolution, heralding
observed in native tumors. Complementary approaches, a new era in precision oncology research.
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such as magnetic levitation 3D culture systems, have
successfully replicated the radial distribution of CD133 4.1.2. Intercellular communication within
+
glioblastoma stem cells and non-stem counterparts, tumor organoids
mimicking their in situ spatial organization. Similarly, Bioprinting allows for the exact positioning of different
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bioprinted pancreatic ductal adenocarcinoma models cell types and biomaterials in a 3D space with the help
demonstrated the self-organization of cancer cells of a mechanical and computer-assisted system to mimic
into heterogeneous aggregates, reflecting the clonal the in vivo spatial architecture of a tissue or tumor
dynamics and spatial complexity of human tumors. and its microenvironment. This facilitates the study of
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bidirectional signaling between cancer cells and stromal
Microfluidic-integrated bioprinting systems permit the components, such as CAFs, immune cells, and endothelial
spatial embedding of vascular endothelial cells, CAFs, cells. A key advantage of bioprinting-based preclinical
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and immune cells within biomimetic matrices, thus cancer models is the standardization of cell deposition,
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establishing oxygen/nutrient gradients that emulate tumor
ecological heterogeneity. Notably, in GelMA hydrogels along with the ability to construct artificial 3D tumors
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containing 10% Matrigel, CAFs self-organize into 50–100 incorporating multiple cell types, structural elements,
µm fibrous bundles, guiding tumor cells along defined and ECM. This capability enhances the potential for more
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invasion trajectories. These engineered architectures accurate personalized medicine strategies. Early research
provide a physiologically relevant platform to investigate primarily utilized bioprinted cancer cell lines or single-cell
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paracrine signaling networks among sub-clonal niches. suspensions to generate such models. More recently,
advancements in dispersing organoids and tumoroids
Integration of fluorescent barcoding with 3D alongside stromal cells have enabled the development of
bioprinting allows real-time tracking of sub-clonal co-culture models that incorporate the TMEs. It also
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spatial dynamics, which enables the quantitative profiling facilitates the construction of vascularized tumor organoids
of spatial heterogeneity. In hepatocellular carcinoma by embedding perfusable channels lined with endothelial
models, serial section imaging revealed epidermal cells, thereby simulating nutrient exchange and immune
growth factor receptor-high subclones preferentially cell trafficking. 39,42,123 Sequential printing of sacrificial inks
colonizing nutrient-rich zones within 300 µm of artificial enables the creation of hierarchical vascular networks that
vasculature, exhibiting a 2.3-fold proliferation advantage support long-term organoid survival and maturation. 42,159
over peripheral populations. 149–151 Spatial transcriptomics The mammary microenvironment has been shown to
further identified elevated Wnt/β-catenin pathway activity suppress tumor progression by redirecting cancer cells to
in these regions, correlating with immunohistochemical adopt a normal mammary epithelial progenitor fate in vivo.
patterns in clinical specimens. 136
However, the mechanism(s) by which this alteration occurs
Bioprinted glioblastoma models with concentric have yet to be defined. A 3D bioprinted fibroblast-mediated
architectures simulate temozolomide diffusion gradients, breast tumor organoid revealed that CAFs enhance ECM
revealing that CD133 cells located 800 µm from drug remodeling and paracrine communication, promoting
+
release sites demonstrated 4.7-fold higher survival rates, tumor stiffness and conferring resistance to radiotherapy.
attributable to hypoxia-induced adenosine triphosphate Similarly, researchers evaluated mitochondrial transfer in
binding cassette subfamily G member 2 upregulation. 3D bioprinted chimeric organoids to test the hypothesis
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Volume 11 Issue 4 (2025) 81 doi: 10.36922/IJB025190184